Prospects for in vivo blood velocimetry using acoustic resolution photoacoustic Doppler

Acoustic resolution photoacoustic Doppler flowmetry (AR-PAF) is a technique that has the potential to overcome the spatial resolution and depth penetration limitations of current blood flow measuring methods. Previous work has shown the potential of the technique using blood-mimicking phantoms, but it has proved difficult to make accurate measurements in blood, and thus in vivo application has not yet been possible. One explanation for this difficulty is that whole blood is insufficiently heterogeneous. Through experimental measurements in red blood cell suspensions of different concentrations, as well as in whole blood, we provide new insight and evidence that refutes this assertion. We show that the velocity measurement accuracy is influenced by bandlimiting not only due to the detector frequency response, but also due to spatial averaging of absorbers within the detector field-of-view. In addition, there is a detrimental effect of limited light penetration, but this can be mitigated by selecting less attenuated wavelengths of light, and also by employing range-gating signal processing. By careful choice of these parameters as well as the detector centre frequency, bandwidth and field-of-view, it is possible to make AR-PAF measurements in whole blood using transducers with bandwidths in the tens of MHz range. These findings have profound implications for the prospects of making deep tissue measurements of blood flow relevant to the study of microcirculatory abnormalities associated with cancer, diabetes, atherosclerosis and other conditions.